Understanding the mechanisms controlling and regulating the DNA replication process in animal cells is fundamental for explanations of normal cell growth and the adnormal growth of cancerous cells. The long range goal of this research is to contribute to that understanding by studying the replication of the herpesvirus origin as a model for cellular DNA replication. In addition, the insight gained from this research may be useful for developing methods to control herpesvirus infections, a significant clinical problem in man. The approach will be to biologically and biochemically analyze the protein-DNA interactions that occur specifically at the HSV-1 origin sequences. The specific objectives are to (1) identify, isolate, and characterize, biochemically and genetically, the viral and/or cellular proteins that interact specifically with the replication origins, (2) determine the effects of changes in the nucleotide sequence of the HSV-1 origins on protein-DNA interactions and on DNA replication, and (3) develop a cell-free system capable of replicating exogenously-added DNA containing an HSV-1 origin of replication.